It is proposed to develop an in vitro model of human pancreas carcinogenesis for the study of cellular evolution leading to human pancreatic neoplasia. Investigation of the differential roles of various cell populations of the pancreas in the activation of chemical carcinogens, promotors and inhibitors of pancreas carcinogenesis will be carried out. The efficacy of culture conditions will be evaluated based on the morphological (LM) and ultrastructural (EM) preservation of the pancreatic explants, and attempts to improve such conditions will be made. Immediate and long-term effects of dimethylnitrosamine (DMNA), methylnitrosourea (MNU) and methylnitrosoguanidine (MNG) on human pancreas explants in culture will be evaluated by light and electron microscopy. Biological behavior of tumors induced in vitro by these carcinogens will be tested in xenogeneic host.